Mechanical strain injury increases intracellular sodium and reverses Na+/Ca2+ exchange in cortical astrocytes

Candace L. Floyd, Fredric A Gorin, Bruce G Lyeth

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Traditionally, astrocytes have been considered less susceptible to injury than neurons. Yet, we have recently shown that astrocyte death precedes neuronal death in a rat model of traumatic brain injury (TBI) (Zhao et al.: Glia 44:140-152, 2003). A main mechanism hypothesized to contribute to cellular injury and death after TBI is elevated intracellular calcium ([Ca 2+]i). Since calcium regulation is also influenced by regulation of intracellular sodium ([Na+]i), we used an in vitro model of strain-induced traumatic injury and live-cell fluorescent digital imaging to investigate alterations in [Na+]i in cortical astrocytes after injury. Changes in [Na+]i, or [Ca2+]i were monitored after mechanical injury or L-glutamate exposure by ratiometric imaging of sodium-binding benzofuran isophthalate (SBFI-AM), or Fura-2-AM, respectively. Mechanical strain injury or exogenous glutamate application produced increases in [Na+] i that were dependent on the severity of injury or concentration. Injury-induced increases in [Na+]1 were significantly reduced, but not completely eliminated, by inhibition of glutamate uptake by DL-threo-β-benzyloxyaspartate (TBOA). Blockade of sodium-dependent calcium influx through the sodium-calcium exchanger with 2-[2-[4-(4-Nitrobenzyloxy)- phenyl]ethyljisothiourea 0mesylate (KB-R7943) reduced [Ca2+] i after injury. KB-R7943 also reduced astrocyte death after injury. These findings suggest that in astrocytes subjected to mechanical injury or glutamate excitotoxicity, increases in intracellular Na+ may be a critical component in the injury cascade and a therapeutic target for reduction of lasting deficits after traumatic brain injury.

Original languageEnglish (US)
Pages (from-to)35-46
Number of pages12
JournalGLIA
Volume51
Issue number1
DOIs
StatePublished - Jul 2005

Keywords

  • Calcium
  • Fura-2
  • Glutamate
  • KB-R7943
  • SBFI-AM
  • TBOA
  • Traumatic brain injury

ASJC Scopus subject areas

  • Immunology

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